The commercial production of therapeutic clinical products containing biological derivatives requires sterilization methods to effectively eliminate bio-burden.
Expanded Human Umbilical Tissue Derived Cells (hUTC) are being developed as a potential cell therapy for the treatment of various degenerative diseases. In addition, cell derivatives (such as trophic factors, proteins, and other molecules) are also being developed as potential therapeutic agents. These derivatives can be used alone or in combination with biomaterials to augment cellular response. Upon deployment directly or indirectly to a target injury site, the derivatives may reduce excessive inflammation, reduce apoptosis and necrosis of endogenous cells of the injury site, induce differentiation of endogenous progenitor cells, increase neovascularization and angiogenesis, and promote new tissue formation. Alone, the derivatives can be deployed as a lyophilized powder, or combined with an aqueous or viscous delivery vehicle. The derivatives can also be combined with and released from biomaterials. For example, the application of the hUTC lysate to biomaterials followed by lyophilization produces a device applicable to tissue engineering and regenerative medicine. Additional information may be found in WO 2005/003334 (filed as PCT/US2004/020931, Jun. 25, 2004), and WO/2006/071794 (filed as PCT/US2005/046851, Dec. 22, 2005), both of which are incorporated herein by reference in their entireties.
However, current methods of sterilization of hUTC and other products containing biological derivatives, while being effective from the sterilization standpoint, reduce the biological activity of the derivatives. Previous approaches have made use of protective agents in combination with the biological sample. See, e.g., U.S. Pat. No. 5,730,933 (disclosing methods that comprise the step of forming a mixture of the biological sample with an extraneous protein, and optionally a free-radical scavenger, prior to irradiation). Such methods have the disadvantage of requiring additional processing steps and materials in addition to the sterilization protocol. Other previous methods perform sterilization in the presence of hydrogen gas. See U.S. 2004/0101958. Improved methods for sterilizing materials that contain active biological derivatives, as well as sterilized yet efficacious clinical products, are needed.